The sudden emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly evolved into a global pandemic, significantly impacting public health, economies, and global biosafety systems. While vaccines and antiviral drugs have been developed, concerns remain about their safety and efficacy, and the ongoing need for effective, affordable, and accessible treatments. This review investigates the potential of animal milk and its components as natural immunomodulators and antivirals to mitigate COVID-19 severity and reduce hospitalizations. Animal milk is a complex fluid containing various bioactive compounds, including proteins, lipids, oligosaccharides, vitamins, and minerals, each potentially playing a role in immune function and viral defense. The review aims to highlight the immunomodulatory, antiviral, anti-inflammatory, and other therapeutic properties of these milk components in the context of viral diseases, particularly COVID-19, and explore their potential use as complementary therapies.

The review comprehensively examines existing literature on the bioactive components of animal milk and their reported effects on immune function and viral infections. Studies focusing on the immunomodulatory and antiviral properties of caseins, whey proteins (including lactoferrin, lactoperoxidase, α-lactalbumin, β-lactoglobulin), milk fats (glycerol monolaurate), carbohydrates (milk oligosaccharides and glycosaminoglycans), vitamins (A, D, E, K, and B complex), and minerals (calcium, phosphorus, magnesium, sodium, potassium, zinc, selenium, iodine, and copper) are synthesized. The review also considers the roles of these components in mitigating inflammation (cytokine storm syndrome), coagulopathy, and oxidative stress associated with severe COVID-19. In silico studies, in vitro experiments, and in vivo trials are integrated to provide a comprehensive overview of the potential benefits of these milk components.

This review followed a systematic approach to gather information from various scientific databases, including PubMed, ScienceDirect, and Google Scholar. Keywords such as "animal milk," "COVID-19," "immunomodulation," "antiviral," "anti-inflammatory," "casein," "whey protein," "lactoferrin," "lactoperoxidase," "oligosaccharides," "glycosaminoglycans," "vitamins," and "minerals" were used to identify relevant studies. The search was restricted to peer-reviewed articles published in English. Inclusion criteria were studies that investigated the biological activity of animal milk components in relation to immune response, viral infections, or inflammatory processes. Studies specifically focusing on SARS-CoV-2 and other coronaviruses were given priority. The selected studies were critically appraised to assess their methodological rigor and the reliability of their findings. Data from in silico, in vitro, and in vivo studies were synthesized and analyzed to provide a comprehensive understanding of the potential benefits of various milk components against COVID-19. A narrative synthesis was used to integrate the findings from different studies and to present a cohesive overview of the topic.

The review revealed that various components of animal milk exhibit multiple properties relevant to COVID-19 management. Caseins and their derived peptides demonstrate immunomodulatory effects by stimulating lymphocyte proliferation, natural killer (NK) cell activity, and antibody formation. Caseins also show antiviral and antithrombotic activities against specific viruses and by inhibiting platelet aggregation, respectively. Whey proteins, particularly lactoferrin and lactoperoxidase, display potent antiviral and anti-inflammatory properties, reducing pro-inflammatory cytokine production and potentially controlling the cytokine storm. Lactoferrin also shows direct antiviral action by binding to viral particles or host cell receptors. Milk oligosaccharides act as prebiotics, promoting a healthy gut and inhibiting pathogen binding. Glycosaminoglycans may also demonstrate antiviral activity. Milk fats, especially glycerol monolaurate, exhibit broad-spectrum antimicrobial activity. Long-chain polyunsaturated fatty acids (DHA and EPA) show immunomodulatory and anti-inflammatory effects, and their specialized pro-resolving mediators may alleviate lung injury. Vitamins (A, D, E, K, and B complex) play vital roles in immune function and mitigating COVID-19 symptoms, and minerals (calcium, phosphorus, magnesium, zinc, selenium, iodine, and copper) are essential for immune response, reducing inflammation, and mitigating complications. The efficacy of these components is often influenced by factors such as the animal species, diet, lactation stage, and processing methods.

The findings suggest that animal milk components offer a multifaceted approach to combating COVID-19. The combined immunomodulatory, antiviral, and anti-inflammatory properties of these compounds could potentially address key aspects of the disease's pathogenesis. The synergistic effects of multiple components, such as the combined anti-inflammatory actions of lactoferrin and lactoperoxidase or the integrated roles of various vitamins and minerals in bolstering immune function, warrant further investigation. These findings support exploring the potential of animal milk, especially when supplemented with targeted nutrients, as a complementary therapeutic approach in COVID-19 management.

This review highlights the potential of animal milk components as a source of naturally occurring bioactive compounds with preventative and therapeutic applications against COVID-19. The synergistic actions of various milk constituents in modulating immune response, reducing inflammation, and exhibiting direct antiviral effects are noteworthy. While further research, including well-designed clinical trials, is essential to confirm these promising findings, the existing evidence suggests that incorporating animal milk and its enriched products into holistic COVID-19 management strategies could be beneficial. Future research should focus on isolating and characterizing specific bioactive peptides, investigating their mechanisms of action, and evaluating their effectiveness in clinical settings.

This review is limited by the available literature on the specific effects of animal milk components on SARS-CoV-2. Many studies are in vitro or in vivo, lacking extensive human clinical trials. The bioavailability and efficacy of these compounds in humans may also vary depending on factors such as individual health status, dosage, and interaction with other medications. The diverse composition of milk from different animal species also needs further study to optimize efficacy. More research into synergistic interactions between milk components is needed.